Reversible induction of mitophagy by an optogenetic bimodular system

被引：33

作者：

D'Acunzo, Pasquale ^{[1
]}

Strappazzon, Flavie ^{[2
,3
]}

Caruana, Ignazio ^{[1
]}

Meneghetti, Giacomo ^{[4
]}

Di Rita, Anthea ^{[2
,3
]}

Simula, Luca ^{[1
,3
]}

Weber, Gerrit ^{[1
]}

Del Bufalo, Francesca ^{[1
]}

Dalla Valle, Luisa ^{[4
]}

Campello, Silvia ^{[2
,3
]}

Locatelli, Franco ^{[1
,5
]}

Cecconi, Francesco ^{[1
,3
,6
]}

机构：

[1] IRCCS Bambino Gesu Childrens Hosp, Dept Paediat Haematol Oncol & Cell & Gene Therapy, Piazza St Onofrio 4, I-00165 Rome, Italy

[2] IRCCS Fdn Santa Lucia, Via Fosso di Fiorano 64, I-00143 Rome, Italy

[3] Univ Tor Vergata, Dept Biol, Via Ric Sci 1, I-00133 Rome, Italy

[4] Univ Padua, Dept Biol, Via Ugo Bassi 58-B, I-35131 Padua, Italy

[5] Sapienza Univ Rome, Dept Gynecol Obstet & Pediat, Piazzale Aldo Moro 5, I-00185 Rome, Italy

[6] Danish Canc Soc, Unit Cell Stress & Survival, Res Ctr, Strandboulevarden 49, DK-2100 Copenhagen, Denmark

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

关键词：

PARKIN GENE; MITOCHONDRIAL; APOPTOSIS; DYSFUNCTION; FCCP; AUTOPHAGY; DEPLETION; AMBRA1; CELLS; MODEL;

D O I：

10.1038/s41467-019-09487-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Autophagy-mediated degradation of mitochondria (mitophagy) is a key process in cellular quality control. Although mitophagy impairment is involved in several patho-physiological conditions, valuable methods to induce mitophagy with low toxicity in vivo are still lacking. Herein, we describe a new optogenetic tool to stimulate mitophagy, based on light-dependent recruitment of pro-autophagy protein AMBRA1 to mitochondrial surface. Upon illumination, AMBRA1-RFP-sspB is efficiently relocated from the cytosol to mitochondria, where it reversibly mediates mito-aggresome formation and reduction of mitochondrial mass. Finally, as a proof of concept of the biomedical relevance of this method, we induced mitophagy in an in vitro model of neurotoxicity, fully preventing cell death, as well as in human T lymphocytes and in zebrafish in vivo. Given the unique features of this tool, we think it may turn out to be very useful for a wide range of both therapeutic and research applications.

引用

页数：13

共 40 条

[1] Ambra1 knockdown in zebrafish leads to incomplete development due to severe defects in organogenesis [J].